DE10101892A1 - Production of polymer capsules with active ingredients for use as controlled-release delivery systems, e.g. for pharmaceuticals, involves non-radical mini-emulsion polymerisation in presence of active ingredient and surfactant - Google Patents

Abstract

A method for the production of polymer capsules, pellets or droplets containing an active ingredient or substance involves non-radical polymerisation of suitable monomers in a mini-emulsion containing the active ingredient(s) and ionic or non-ionic surfactant(s). A method for the production of polymer capsules, pellets or droplets (PC) containing an active ingredient or substance involves: (a) preparation of a mini-emulsion containing monomers (I) which are polymerizable by non-radical emulsion polymerisation, active ingredient(s) or substance(s) (II) and surfactant(s) (III) to stabilize the mini-emulsion, especially non-ionic surfactants (preferably non-polymeric, preferably low-mol. wt.) or ionic surfactants; (b) performing non-radical polymerisation with in-situ encapsulation or inclusion of component (II); and (c) optionally isolating the PC. Independent claims are included for: (1) a method for the production of (PC) by: (a) preparation of a mini-emulsion containing di- or poly-functional epoxide(s), isocyanate(s) or carboxylic acid anhydride(s) (monomer I'), compound(s) which undergo polyaddition reactions with (I') (monomer I''), and components (II) and (III) as above; (b) performing a poly-addition reaction between (I') and (I'') in the mini-emulsion, with in situencapsulation etc. as above; and (c) optionally isolating PC; (2) polymer capsules etc. with an active ingredient (PC) as obtained by this method; (3) PC as described above, with active ingredient(s) or substance(s) in the polymer matrix forming the capsules etc., in which the wall layers consist of a polymer obtained by non-radical mini-emulsion polymerisation, especially polycondensation, polyaddition or homopolymerization of suitable monomers, and the active ingredient is preferably a hydrophobic or amphiphilic substance which is homogeneously miscible with the monomer system; and (4) cosmetics, body care products, pharmaceuticals, hygiene products, food, adhesives, detergents/cleaning agents and packaging containing PC.

Description

The present invention relates to processes for producing active or active polymer capsules, beads or droplets containing substances due to non-radicals cal miniemulsion polymerization and the use of in this way manufactured capsules, beads or droplets as delivery systems for Active ingredients, especially for use in cosmetic products, pharmaceutical compositions, adhesives, washing and cleaning means and the like.

Active substances or active substances such as fragrances, essential oils, perfume oils and care oils, dyes or pharmaceutically active ingredients that are in kos metallic and / or pharmaceutical products or in washing and cleaning agents are often used during storage or but directly when applying their activity. Some of these substances can also have insufficient stability for use or are disruptive Cause interactions with other product components.

Therefore, it is of interest to control such substances and at the desired one Use location with maximum effect.

For this reason, active or active substances such as fragrances, care products oil and antibacterial agents in the products in spatially delimited, protected form added. Sensitive substances are often described in Chap Included in various sizes, on suitable substrates adsorbed or chemically modified. The release can then be carried out with the help of an egg A suitable mechanism can be activated, for example mechanically by shear, or diffusely directly from the matrix material.

Therefore, systems are sought that are encapsulation, transportation or Presentation vehicle - often synonymous as "delivery systems" or "car rier systems "- suitable.

There are already numerous commercial delivery systems that are based on po based polymer particles or liposomes (e.g. Mikrosponges® from from Advanced Polymer Systems or Nanotopes® from the company  Ciba-Geigy, see in this regard B. Herzog, K. Sommer, W. Baschong, J. Röding "Nanotopes ™: A Surfactant Resistant Carrier System" in the SÖFW Journal, 124th year 10/98, pages 614 to 623).

The disadvantage of this conventional, known from the prior art Delivery systems consist in that they have a low loading potential have, the particle size of the polymer balls usually in the range of a few Micrometers to a few 100 microns and encapsulation of the active sub punching can usually not be done in situ. The modification of chap Sel surface is not possible or very expensive. Liposomes also have also insufficient stability for many applications.

K. Landfester, F. Tiarks, H.-P. Hentze, M. Antonietti "Polyaddition in mini emulsions: A new route to polymer dispersions "in Macromol. Chem. Phys. 201, 1-5 (2000) generally describe polyadditions in mini-emulsions. Encapsulation of active ingredients is not mentioned there.

A general procedure for performing polyaddition reactions in Mini emulsions are also described in WO 00/29465.

The European patent application EP 0 967 007 A2 describes a method ren for microencapsulation of solid, biologically active substances, in particular Pesticides, by polycondensation of a melamine or phenol / formaldehyde Resin or a urea / formalin resin in dispersion in the presence of the each to be encapsulated active substance and a nonionic polymer Protective colloids to stabilize the emulsion, microcapsules with average particle diameters of 0.1 to 300 microns can be obtained. This The method is only suitable for encapsulating solid biological active substances net. To stabilize the emulsion, the emulsion must be polymeric Protective colloid can be added.

Y. G. Durant "Miniemulsion Polymerization: Applications and Continuous Process "in Polymer. Mater. Sci. Eng. 1999, 80, pages 538-540 describes the Encapsulation of organically soluble dyes with a polymer shell made of poly styrene by UV-induced radical polymerization of styrene in mini emulsion. Encapsulation of compounds other than organically soluble Dyes are not mentioned. A disadvantage of this method is in particular  that relatively sensitive connections do not ver can be encapsulated because the interme diically formed radicals more sensitive compounds, e.g. B. those with dop fur bonds, can attack.

B. Erdem et al. "Encapsulation of Inorganic Particles via Miniemulsion Po lymerization "in Polymer. Mater. Sci. Eng. 1999, 80, pages 583/584 ben encapsulation of solid, insoluble inorganic particles, namely Ti tandioxide particles, with a polymer shell made of polystyrene by UV-induced radical polymerization of styrene in a miniemulsion. An encapsulation compounds other than insoluble, solid inorganic particles will not mentioned. A disadvantage of this method is that it is relatively sensitive Connections cannot be encapsulated using this method because the radicals em. intermediately formed in the radical polymerization more sensitive compounds, e.g. B. can attack those with double bonds NEN.

WO 98/02466, DE 196 28 142 A1, DE 196 28 143 A1 and EP 818 471 A1 write the production of aqueous polymer dispersions by free radical polymerization of radically polymerizable compounds in Condition of the miniemulsion. There is no encapsulation of active substances mentioned earlier.

DE 44 36 535 A1 describes a method for producing microcapsules dispersions described by interfacial polyaddition, which under US of special oil-soluble emulsifiers (fatty acid esters, fatty amides, poly glycol ether or polypropylene glycol ether) with a certain minimum solubility works in the oil phase.

US-A-4 626 471 describes a process for the microencapsulation of colorless organic dye precursor molecules by in-situ polymeri sation of polyfunctional amines with special multifunctional epoxyhar zen based on methylolated bisphenol-A or 4-glycidyloxy-N, N- diglycidylaniline.  

It is now the object of the present invention to provide a method for Preparation of polymeric capsules, beads or droplets len, which are suitable as carriers for active ingredients of various types. In particular, the method should also encapsulation or inclusion sensitive active ingredients or active ingredients that come with her conventional methods cannot be encapsulated or cannot be encapsulated easily NEN.

Due to the encapsulation, coagulation, agglomeration or uncon controlled diffusion of the enclosed active substances or active substances prevented while allowing their controlled release.

The polymeric capsules, beads produced by such a method or droplets should continue to have the largest possible loading potential tial. In particular, they are intended as carrier or delivery systems for Various types of active ingredients can be used and so ensure with their controlled release at the desired location.

Furthermore, such a method is intended to modify the particles in a targeted manner enable properties for their respective use. That is in particular This is important if the particles are targeted at the location of the user or an intrinsic affinity for the location itself should have their application.

Another object of the present invention is that which is based on the applicant herself declining German patent application 100 37 656.6 with the filing date of July 31, 2000 develop, in particular to optimize.

According to a first embodiment, the present invention relates to a process for producing polymer capsules, beads or droplets containing active ingredient or active ingredient, which comprises the following process steps:

• a) Provision of a mini emulsion comprising:
  • compounds polymerizable by non-radical emulsion polymerization (monomers),
  • - at least one active or active ingredient to be encapsulated or enclosed and
  • - At least one surface-active substance (surfactant) for stabilizing the miniemulsion, in particular selected from the group of
    • a) nonionic surfactants, especially non-polymeric, preferably low molecular weight nonionic surfactants, and
    • b) ionic surfactants;
• b) carrying out a non-radical polymerization reaction in the miniemulsion provided in step (a), thereby resulting in an In-situ encapsulation or in-situ confinement of the active ingredient in the poly produced by non-radical polymerization reaction capsules, globules, or droplets; and
• c) then, if appropriate, separating off the products obtained in this way polymer capsules or spheres containing active ingredient or active ingredient -droplet,

the active ingredient being hydrophobic or amphiphilic and dealing with allows the monomer system to mix homogeneously.

The applicant has now surprisingly found that this is the case Process according to the invention for the production of active or active substance-containing poly Mercury capsules, globules or droplets by mini-emulsion polymerization suitable starting monomers leads to good results, if the active ingredient is hydrophobic or amphiphilic and deals with allows the monomer system to mix homogeneously. In other words, the hydrophobic or amphiphilic active ingredient with a view to that Monomer system selected such that active or active ingredient and mono form a homogeneous single-phase mixture. This must be for everyone Active or active ingredient - for a given monomer system - separately be checked. In other words, on the one hand, it becomes an active ingredient and on the other hand, monomers to be polymerized in such a way true that they can be mixed homogeneously, d. H. a homogeneous single phase Form mixture.

The hydrophobic or amphiphilic active ingredient is preferably used in the Selected with regard to the polymer system produced in step (b) in such a way that it can be mixed homogeneously with it, d. H. in other words single-phase homogeneous mixture also forms with this. This must also be done for everyone Active or active ingredient can be checked separately. In other words, ge according to a preferred embodiment of the hydrophobic or amphiphilic Active ingredient selected such that it is on the one hand in front of the Polymerisa tion with the monomer system and on the other hand after the polymerization with  the resulting polymer system is in each case homogeneously miscible or in each case forms a homogeneous single-phase mixture. According to this preferred Embodiment are active or active ingredient on the one hand and polymeri based monomers, on the other hand, matched to one another such that the Active or active itself with both the starting monomers and allows the resulting polymer to mix homogeneously, d. H. a ho mogeneous single-phase mixture.

The representation of the active or active substance-containing carrier according to the invention system (polymer capsules, beads or droplets) takes place according to the invention according to a non-radical polymerization in a so-called miniemul sion.

Mini emulsions are dispersions of an aqueous phase, an oil phase and optionally one or more surface-active substances which are used to realize unusually small droplet sizes. Miniemulsio In other words, as an aqueous dispersion, stable oils can be used droplets with drop sizes of about 10 to about 500 nm understood those obtained by intensive shearing of a system that contains oil, Contains water, a surfactant and a hydrophobic. The hydrophobes for the Production of stable miniemulsion are required, for example Mo nomers, which have a low water solubility. The hydrophobic suppresses the mass exchange between the different oil droplets by osmotic forces (Ostwald ripening), but directly after the Mini emulsion formation, the dispersion is only critically stabilized with regard to Collisions of the particles, and the drops themselves can still be sized grow through further bumps and fuses.

Unlike microemulsions, which are generally called thermodyna mix stable and optically transparent emulsions with droplet sizes of generally about 2 to at most about 50 nm, which is obtained by mixing Water, oil, surfactant and optionally cosurfactant are prepared Mini emulsions can be considered kinetically stable and optically opaque to cloudy emulsions with droplet sizes generally of about 10 up to about 500 nm can be understood, which by mixing water, oil, Surfactant and optionally cosurfactant and optionally a (further) Hydrophobic (e.g. also an oil) due to the introduction of relatively high amounts of shear energy are produced, the droplet size in the mini emulsion  especially through the energy input and the type and quantity of each Components, in particular the surfactants and optionally cosurfactants, be is true. In contrast to conventional emulsions, they are Droplet size distributions in mini-emulsions almost monodisperse. In all common are mini emulsions - in contrast to microemulsions - kri stabilized table, d. H. a proportion of surfactant is generally required which just enough to stabilize the systems, especially a surfactant part of less than 5 wt .-%, while in the case of microemulsions required surfactant content is about 5 to 15 wt .-% significantly higher. Of Furthermore, the interfacial tension in miniemulsions is significantly higher than for microemulsions.

Further details regarding mini emulsions and polymerizations in Mini emulsions are referred to the article by K. Landfester, F. Tiarks, H.-P. Hentze, M. Antonietti "Polyaddition in miniemulsions: A new route to polymer dispersions "in Macromol. Chem. Phys. 201, 1-5 (2000), whose In is hereby incorporated by reference. Reference is also made to the publication E. D. Sudol, M. S. Es-Aasser, cited there, in: "Emulsion Polymerization and Emulsion Polymers ", P.A. Lovell, M.S. El-Aasser, Eds., Chichester 1997, p. 699, the contents of which are also hereby incorporated by reference is included. Furthermore, reference can be made to WO 00/29465 the, the process for carrying out polyaddition reactions in mini describes emulsions and their content also by reference is involved.

In method step (a) of the method according to the invention takes place first the provision or manufacture of the mini used according to the invention emulsion.

The microemulsion is prepared in a manner known per se. It can be referred to the previously cited references, namely the Article by Landfester et al., The Sudol et al. as well as to the already cited WO 98/02466, DE 196 28 142 A1, DE 196 28 143 A1 and EP 818 471 A1.

To produce the mini emulsion is first known in a simple way ter produced an aqueous macroemulsion containing the monomers, the active ingredient to be encapsulated and the surfactant (surfaces active substance).  

After the mixture is homogenized and transferred to a macro emulsion the macroemulsion formed in this way is subsequently converted into in a conventional manner known to the person skilled in the art into a so-called mini emulsion, a very stable type of emulsion, e.g. B. by treatment of Macro emulsion previously generated by ultrasound, by high pressure homogeneity nization or through a microfluidizer. The fine distribution of the components ten is generally achieved by a high local energy input.

The mini emulsion used according to the invention is a essentially aqueous stabilized by the surfactant Emulsion of monomers and active or active ingredient (s) with a particle size of the emulsified droplets from 10 nm to 500 nm, in particular from 40 nm to 450 nm, preferably from 50 nm to 400 nm.

The average size of the droplets of the disperse phase of the invention Mini emulsion used can generally be based on the principle of determine quasi-elastic dynamic light scattering, with the so-called z-average droplet diameter of the unimodal analysis of the Autocorrelation function is obtained.

The particle size and particle size distribution of the emulsified droplets Finally, the particle size and part also determine in the miniemulsion size distribution of the polymerized end products and is correct hereby agree. The polymer particles obtained can also Using dynamic light scattering in terms of their particle size and Monodispersity can be characterized.

The monomers used according to the invention are generally mean polymerizable by non-radical emulsion polymerization Compounds (monomers). In particular, these are Monomers by polycondensation, especially by poly addition reaction, are polymerizable.

In general, the monomers used in the invention are hydrophobic or amphiphilic. In addition, the monomers can be encapsulated with the mix the hydrophobic or amphiphilic active ingredient homogeneously, d. H. hereby form a homogeneous single-phase mixture.

In particular, the monomers used according to the invention are essential Lichen insoluble in water or at least only sparingly soluble in the aqueous phase.  The monomers used according to the invention are preferably in the aqueous phase to less than 10%, preferably less than 5%, esp especially less than 1%, soluble.

In general, the monomer content is that provided in step (a) Mini-emulsion in the range from 1 to 45% by weight, preferably 3 to 25% by weight, in particular 5 to 15 wt .-%, based on the miniemul sion.

As mentioned above, the method according to the invention is to be used closing or encapsulating active or active ingredient hydrophobic or amphiphilic. Furthermore, the hydrophobic or amphiphilic active or Active ingredient selected such that it is homogeneous with the monomer system can mix, preferably also with the polymer produced in step (b) system.

In particular, the one to be included by the method according to the invention or active ingredient to be encapsulated is essentially water-insoluble or at least only sparingly soluble in the aqueous phase. Generally is less than 10% of the active ingredient in the aqueous phase preferably less than 5%, especially less than 1%, soluble. Je ge the lower the degree of water solubility, the better the general Encapsulability of the active ingredient.

The active ingredient used according to the invention should be in organic Media and solvents, especially in the monomers, soluble or be dispersible.

The active ingredient can either be used under reaction conditions as Liquid or as a solid.

The active ingredient is preferably selected from the group of Fragrances; Oils such as essential oils, perfume oils, care oils and silicone oil; pharmaceutically active substances such as antibacterial, antiviral or fungicidal active ingredients; Antioxidants and biologically active substances; Vitamins and vitamin complexes; Enzymes and enzymatic systems; cosmetically active substances; substances active in washing and cleaning; biogenic agents and genes; Polypeptides and viruses; Proteins and lipids; Waxing and fats; Foam inhibitors; graying and color protection agents; Soil-repellent active ingredients; Bleach activators and optical brighteners; amines; and mixtures of those listed above  Compounds, especially mixtures with dyes or coloring Substances.

The active or active ingredient content in the mini provided in step (a) emulsion is generally 0.01 to 45% by weight, preferably 0.1 to 30% by weight, in particular 1 to 20 wt .-%, based on the mini emulsion.

According to the first embodiment of the present invention, the surface-active substance (surfactant) used to stabilize the mini-emulsion is particularly selected from the group of

• a) ionic surfactants, especially non-polymeric, preferably lower molecular nonionic surfactants, and
• b) ionic surfactants.

If the surfactant used in the invention (surfactant) to stabilize the miniemulsion (i) a non-polymeric, in particular never is the molecular nonionic surfactant, it can be selected in particular are from the group of alkoxylated, preferably ethoxylated fat alcohols, alkylphenols, fatty amines and fatty acid amides; alkoxylated Triglycerides, mixed ethers and mixed formals; optionally partially oxi dated alk (en) yl oligoglycosides; Glucoronsäurederivaten; Fatty acid-N-alkyl glucamides; Protein hydrolyzates, especially alkyl-modified protein hy drolysaten; low molecular weight chitosan compounds; Zuckerestern; sorbitan esters; Amine oxides.

If the surfactant used in the invention (surfactant) to stabilize the miniemulsion (ii) is an ionic surfactant, it can act as a cationic or anionic surfactant.

Examples of cationic surfactants suitable according to the invention are such ver bonds that are selected in particular from the group of quaternaries Ammonium compounds such as dimethyldistearylammonium chloride, Stepantex VL 90 (Stepan); Esterquats, especially quaternized fatty acid trialkanol amines ters salted meats; Salts of long chain primary amines; quaternary ammoni compounds such as hexadecyltrimethylammonium chloride (CTMA-Cl); de hyquart A (cetrimonium chloride, Cognis) or Dehyquart LDB 50 (Lauryl dimethylbenzyl; Cognis).  

Examples of anionic surfactants suitable according to the invention are such ver bonds selected in particular from the group of soaps; alkylbenzenesulfonates; alkane; olefin; Alkylethersulfona th; Glycerinethersulfonaten; α-methyl ester sulfonates; sulfofatty; alkyl sulfates; fatty alcohol; glycerol ether; fatty acid ethers sulfates; hydroxy mixed; Monoglyceride (ether) sulfates; fatty acid amide (ether) sulfates; Mono- and dialkyl sulfosuccinates; Mono- and dialkyl sulfosuccinamates; sulfotriglycerides; amide soaps; Ether carboxylic acids and their salts; Fettsäureisothionaten; Fettsäuresarcosinaten; fatty acid taurides; N-acylamino acids such as acyl lactylates, acyl tartrates, acyl glutamates and acyl aspartates; oligoglucoside sulfates; Protein fatty acid condensates, ins special vegetable products based on wheat; Alkyl (ether) phosphates.

The surfactant content provided in step (a) ten miniemulsion is generally 0.1 to 15 wt .-%, preferably 0.3 to 10 wt .-%, in particular 0.5 to 5 wt .-%, based on the Mini emulsion.

The production of the miniemulsion in process step (a) of the invention The method then closes in step (b) tion of a non-radical polymerization reaction in the step (a) provided mini emulsion, thereby encapsulating in situ or an in-situ inclusion of the active ingredient in the by nonradi Kalische polymerization reaction produced polymer capsules, beads or droplet is caused

As previously described, particle size and particle size are determined Division of the emulsified droplets in the mini emulsion, the particle size and Particle size distribution of the polymerized end products and is correct in essentially coincide with this. The polymer particles obtained can with Using dynamic light scattering in terms of their particle size and Monodispersity can be characterized.

In particular, the non-radical polymerization reaction is a polycon densation reaction, preferably a polyaddition reaction.  

In general, the reaction temperatures for the polymerization are especially polycondensation, preferably polyaddition, about 20 to 100 ° C, preferably about 40 to 90 ° C, especially about 50 to 80 ° C.

The reaction time is about 0.01 to about 24 h, in particular about 0.1 to 10 hours, preferably about 1 to about 5 hours.

The polymerization can be by thermal treatment or equivalent chemical processes or initiators are induced. If necessary a suitable reaction accelerator can be added.

The fact that the polymerization is non-radical has a counterpart radical encapsulation known from the prior art development process the advantage that, according to the invention, sensitive active or active ingredients can be encapsulated or enclosed.

Process steps (a) and (b) can either be discontinuous or but can be carried out continuously (e.g. as a batch process).

Process step (b) can optionally be followed by a process step (c) connect, in which the active or active ingredient obtained in step (b) Polymer capsules, beads or droplets with known, the expert common methods can be separated or isolated. Here should no excessive shear forces on the polymer capsules, beads or -Droplets are exerted so that they are not damaged. Fiction suitable separation methods are, for example, freeze drying (Lyophilization) or spray drying under gentle conditions.  

According to a second, special embodiment of the present invention, the subject of the present invention is also a process for the production of polymer capsules, beads or droplets containing active ingredients by miniemulsion polyaddition, the process comprising the following process steps:

• a) Provision of a mini emulsion comprising:
  • at least one di- or polyfunctional epoxide or isocyanate (monomer I),
  • at least one compound which reacts with the di- or polyfunctional epoxide or isocyanate (monomer I) with polyaddition (monomer II),
  • - at least one active or active ingredient to be encapsulated or enclosed and
  • - At least one surface-active substance (surfactant) for stabilizing the miniemulsion;
• b) carrying out a polyaddition reaction between the monomers I and II in the presence of the active to be encapsulated or enclosed or active ingredient and the surfactant in the under Step (a) provided miniemulsion, whereby an in situ Encapsulation or an in-situ inclusion of the active ingredient in the polymer capsules, beads or produced by polyaddition droplet is caused; and
• c) then, if appropriate, separating off the products obtained in this way polymer capsules or spheres containing active ingredient or active ingredient -droplet,

characterized in that the active ingredient or hydrophobic or am is phiphile and can be mixed homogeneously with the monomer system.

As before for the inventive method according to the first embodiment form, the applicant has - also with regard to the invention appropriate method according to the second embodiment - more surprising wise found that this method leads to good results nissen leads if the active ingredient is hydrophobic or amphiphilic and homogeneous with the monomer system (starting monomers I and II) can mix. In other words, the hydrophobic or amphiphilic Active or active in terms of the monomer system so out chooses that active or active ingredient and monomer system a homogeneous single phase  Form mixture. This must be done for each active or active ingredient - at ei given monomer system - be tested separately. In a different way presses, active or active ingredient on the one hand and Mo to be polymerized nomere, on the other hand, are coordinated with each other in such a way that they are ho let it mix, d. H. form a homogeneous single-phase mixture.

The hydrophobic or amphiphilic active ingredient is preferably used in the With regard to the polymer system produced in step (b) - in particular Epo xide resins (formed from the polyaddition of amine, alcohol, mercaptan or Acid anhydride and epoxy), polyurethanes (formed from the polyaddition of Alcohol and isocyanate) and polyureas (formed from the polyaddition of Amine and isocyanate) - selected such that it is homogeneous with it lets mix, d. H. in other words a single phase homogeneous mixture also forms with the polymer system. This must also for every active or Active ingredient to be checked separately. In other words, according to a be preferred embodiment of the hydrophobic or amphiphilic active or Active ingredient selected such that it is on the one hand before the polymerization with the Monomer system and on the other hand after the polymerization with the result polymer system is homogeneously miscible or a homo gene single-phase mixture forms.

In process step (a) of the second embodiment of the invention The first step in the process is the provision or production of the inventions miniemulsion used in accordance with the invention. To do this, refer to the above guided tours.

As in the first embodiment of the method according to the invention, so it is also the mini-emulsion according to the second embodiment form of the process according to the invention by an essentially aqueous, emulsion of monomers stabilized by the surfactant and active ingredient (s) with a particle size of the emulsified droplet Chen from 10 nm to 500 nm, in particular from 40 nm to 450 nm, preferred from 50 nm to 400 nm. For further details, refer to the above referred to the first embodiment.

With regard to the according to the second embodiment of the invention Processes for encapsulating active ingredients can be based on the above statements  with respect to the first embodiment of the invention Procedure are referred.

As mentioned above, the method according to the invention is to be used closing or encapsulating active or active ingredient hydrophobic or amphiphilic. Furthermore, the hydrophobic or amphiphilic active or Active ingredient selected such that it is homogeneous with the monomer system can mix, preferably also with the polymer produced in step (b) system.

In particular, the one to be included by the method according to the invention or active ingredient to be encapsulated is essentially water-insoluble or at least only sparingly soluble in the aqueous phase. Generally is less than 10% of the active ingredient in the aqueous phase preferably less than 5%, especially less than 1%, soluble. Je ge the lower the degree of water solubility, the better the general Encapsulability of the active ingredient.

The active ingredient used according to the invention should be in organic Media and solvents, especially in the monomers, soluble or be dispersible.

The active ingredient can either be used under reaction conditions as Liquid or as a solid.

The active ingredient is preferably selected from the group of Fragrances; Oils such as essential oils, perfume oils, care oils and silicone oil; pharmaceutically active substances such as antibacterial, antiviral or fungicidal active ingredients; Antioxidants and biologically active substances; Vitamins and vitamin complexes; Enzymes and enzymatic systems; cosmetically active substances; substances active in washing and cleaning; biogenic agents and genes; Polypeptides and viruses; Proteins and lipids; Waxing and fats; Foam inhibitors; graying and color protection agents; Soil-repellent active ingredients; Bleach activators and optical brighteners; amines; and mixtures of those listed above Compounds, especially mixtures with dyes or coloring Substances.

Also according to the second embodiment of the method according to the invention The active or active substance content should be in the range provided in step (a) Mini emulsion 0.01 to 45 wt .-%, preferably 0.1 to 25 wt .-%, esp special 1 to 15 wt .-%, based on the mini emulsion.  

In general, according to the second embodiment of the invention monomers I and / or II used according to the method are hydrophobic or amphiphilic. Otherwise, the monomers I and II can be encapsulated with the selenden hydrophobic or amphiphilic active or active ingredient homogeneous mi little, d. H. hereby form a homogeneous single-phase mixture.

In particular, the monomers I and / or II are essentially water-free soluble or at least sparingly soluble in the aqueous phase. virtue as the monomers I and / or II in the aqueous phase are less than 10%, preferably less than 5%, especially less than 1%, soluble.

The requirement for the formulation of the miniemulsion is that the components for the polyaddition reaction (monomers I and II) should show a relatively low solubility in water, in particular at least one of these compounds preferably having a solubility of less than 10 ^-5 g / l should show.

The content of monomers I and II in the mini provided in step (a) emulsion is generally 1 to 45% by weight, preferably 3 to 25% by weight, in particular 5 to 15 wt .-%, based on the mini emulsion. there can the molar ratio of monomers I to monomers II in general NEN in particular 2: 1 or even larger to be already with difunctional monomers to achieve cross-linking and chains Avoid breaks and high molecular weights of the polymer network to generate so that no disturbing residual monomer remains. To this Ways can - as in the case of difunctional amines Monomers II - both react amine hydrogens. Alternatively, you can but the molar ratio of monomers I to monomers II also down too stoichiometric (i.e. 1: 1) or even less.

By varying the chemical nature, especially the functionality, and the amounts of the monomers I (epoxides or isocyanates) and the addi tion compounds (monomers II) can the particle sizes of the emulsified Particles and thus the end product can be controlled in a targeted manner. Furthermore this allows the particle properties of the end products, such as glass temperature and capsule stability, control using polyfunction neller connections in general to higher glass temperatures and stabilization lead the resulting products.  

The hydrophobic, necessary for the production of stable miniemulsion are, in particular, the monomers I themselves, in particular epoxides or Isocyanates because of their low water solubility. Under However, the stability can be increased by adding additional hydrophobes the miniemulsion can still be improved. Ideally, this can be done at for example, the active ingredients to be encapsulated.

As described above, according to the second embodiment, the above lying inventions as monomers I di- or polyfunctional epoxides Come into play. Mixtures of such Epo are very particularly preferred xides, especially mixtures of difunctional and polyfunctional epoxides.

Due to the content of polyfunctional epoxides in the starting mixture can the degree of crosslinking and thus the glass transition temperature of the resulting Control polymers. This leads to a variation in the polymer structure in the polymerized end product, using polyfunctional Epoxides, such as trifunctional and / or tetrafunctional epoxides, together men with difunctional epoxides generally have greater crosslinking achieved greater capsule stability and smaller particle size of the end products becomes.

The epoxides (monomers I) used in accordance with the second embodiment of the method according to the invention can be, for example, di-functional epoxides, for example epoxides derived from bisphenol A, such as bisphenol A diglycidyl ether, or epoxides of the type chlorohydrin-substituted bisphenols, such as z. B. the epoxy of the formula

Such an epoxy with a degree of polymerization of 1 to 2 is e.g. More colorful of the name Epikote E 828® commercially available from Shell.

In the method according to the second embodiment of the invention The epoxides (monomers I) used can also be poly act functional epoxides, for example tri- and / or tetrafunktio contain epoxies. The use of polyfunctional epoxies leads to a variation of the polymeric structure in the polymerized end product, whereby  generally stronger networking with greater capsule stability and smaller particle size of the end products is achieved.

As mentioned above, mixtures of di- and polyfunctional epoxides are used as monomer system I. By the The proportion of di- and polyfunctional compounds can be targeted to the egg Control properties of the resulting capsules, especially cross-linking degree, glass transition temperature, capsule stability and particle size.

A trifunctional epoxide which is suitable according to the invention is, for example, the epoxide of the general formula

(e.g. Denacol Ex-314® from Shell).

A tetrafunctional epoxide suitable according to the invention is, for example, the epoxide of the general formula

(e.g. Denacol Ex-411® from Shell).

If according to the second embodiment of the present invention Monomer I is a di- and / or polyfunctional epoxy, can with the di- and / or polyfunctional epoxy (s) reacting with polyaddition Compound (monomer II) in particular can be selected from the group of (i) di- and polyfunctional amines and their mixtures, (ii) di- and polyfunctional alkanols and their mixtures, (iii) di- and polyfunction nell mercaptans and their mixtures, (iv) di- and polyfunctional Carboxylic anhydrides and their mixtures and (v) mixtures of the before mentioned connections.

In particular, mixtures of difunctional and polyfunctional monomers ren II (amines, alkanols, mercaptans, carboxylic anhydrides and the like)  used. Due to the proportion of difunctional and polyfunctional compound the properties of the resulting capsules can be controlled in particular the degree of crosslinking, glass transition temperature, capsule stability and part size in the measure.

If the monomer II is a di- or polyfunctional amine, it can in particular be selected in particular from the group of (i) optionally substituted alkyldiamines, in particular those with terminal amino groups such as 1,12-diaminododecane or optionally cyanoethylated trimethyl hexamethylenediamines; (ii) optionally substituted bis (aminocycloalkyl) alkanes such as 4,4'-diaminodicyclohexylmethane or isophoronediamines; (iii) optionally substituted bis (aminoaryl) alkanes such as 4,4'-diamino bibenzyl or 4,4'-diaminodiphenylmethane; (iv) Polyoxyalkylene diamines with molecular weights of up to about 5,000 g / mol, in particular polyoxyalkylene diamines with polyoxyethylene and / or polyoxypropylene units, the amino groups preferably being terminal (e.g. Jeffamine D 2000®, an NH ₂ -terminated polypropylene oxide of the general Formula NH ₂ - [CH (CH ₃ ) -CH ₂ -O] _n -CH (CH ₃ ) -CH ₂ -NH ₂ with an average molecular weight of 2,032 g / mol); (v) trifunctional amines (e.g. JEFFAMINE® T-403) and tetrafunctional amines such as N, N, N ', N'-tetraglycidyldiamino-4,4'-diphenylmethane or corresponding multifunctional prepolymers; (vi) polyfunctional amines such as chitosan and chitosan derivatives, polyethylene lenimines, polydiallyldimethylammonium chloride (poly-DADMAC) and the reaction products of polylactides or polyglycolites with isophorone diisocyanate.

When using polyfunctional amines, e.g. B. tri- or tetrafunctional Amines (such as JEFFAMINE® T-403), as explained above, can be a similar Achieved effect in terms of degree of crosslinking, particle size and stability as in the case of trifunctional and tetrafunctional epoxies.

For all reactions involving amines as monomer II, the pH to be higher than 9 to 10 to ensure the solubility of the amine in the continuous lower phase.

If the monomer II is a di- or polyfunctional alkanol, it can for example, 2,2-bis (4-hydroxyphenyl) propane (bisphenol A) or des act homologues or derivatives.  

If the monomer II is a difunctional or polyfunctional mercaptan, it can in particular are selected from the group of optionally substituted ized alkyldithiols (dithioalkanes), preferably those with terminal Thiol groups (SH groups) such as 1,6-hexanedithiol.

As described above, according to the second embodiment, the above lying inventions as monomers I also di- or polyfunctional Isocya nate are used. Mixtures of sol are very particularly preferred cher isocyanates, especially mixtures of di- and polyfunctional Isocyanates.

Due to the content of polyfunctional isocyanates in the starting mixture can the degree of crosslinking and thus the glass transition temperature of the resulting Control polymers. This leads to a variation in the polymer structure in the po lymerized end product, using polyfunctional Isocyanates, such as trifunctional and / or tetrafunctional isocyanates together with difunctional isocyanates generally a stronger crosslinking tion with greater capsule stability and smaller particle size of the end pro products is achieved.

As mentioned above, mixtures of di- and polyfunctional isocyanates are used as monomer system I. By the proportion of di- and polyfunctional compounds can be targeted Control properties of the resulting capsules, especially crosslinking degree, glass transition temperature, capsule stability and particle size.

If a di- and / or polyfunctional isocyanate is used as monomer I. is that with the di- or polyfunctional isocyanate under Polyaddi tion-reacting compound (monomer II) selected in particular from the Group of (i) di- and polyfunctional amines and their mixtures, (ii) di- and polyfunctional alkanols and their mixtures and (iii) Mi of the aforementioned compounds.

When using amines as monomers II result as polyaddi tion products polyureas. With regard to di- and polyfunctional amines can be referred to the above statements. Mixtures of such amines, in particular mixtures, are particularly suitable of di- and polyfunctional amines. Due to the content of polyfunction nelle amines in the starting mixture, the degree of crosslinking and thus control the glass transition temperature of the resulting polymer.  

When using alkanols (alcohols) as monomers II result as polyadducts, polyurethanes. Appropriate with regard to the invention Neter di- and polyfunctional alkanols can ver on the above statements be shown. Mixtures of such alkanols are particularly suitable, in particular special mixtures of di- and polyfunctional alkanols. By Ge hold on polyfunctional alkanols in the starting mixture Degree of crosslinking and thus the glass transition temperature of the resulting polymer Taxes.

As previously explained, by varying the chemical nature, esp special functionality, and the respective amounts (ratios) of the mono mere I (di- and / or functional epoxides or isocyanates) and the addi tion compounds (monomers II, especially di- and / or polyfunctional Amines, mercaptans, alcohols, carboxylic acid anhydrides and the like) Particle size of the emulsified particles and thus of the end product and also the other properties of the resulting capsules (in particular Degree of crosslinking, glass transition temperature and capsule stability) the.

For the formulation of the inventions according to the second embodiment Mini emulsions used according to the process according to the invention can contain anionic, cationic and nonionic surfactants (surface-active or interfaces active substances) can be used in defined quantities. Dependent on the particle size of the emulsified can depend on the type and amount of the surfactant Particles and thus the end product can be varied in a targeted manner.

According to the second embodiment of the method according to the invention As nonionic surfactants, both non-polymeric (low molecular weight) as well as polymeric nonionic surfactants can be used. Not suitable Ionic surfactants according to the second embodiment of the invention his methods are particularly selected from the group of (i) low molecular weight, non-polymeric nonionic surfactants such as alkoxy gated, preferably ethoxylated fatty alcohols, alkylphenols, fatty amines and fatty acid amides; alkoxylated triglycerides, mixed ethers and mixed formal; optionally partially oxidized alk (en) yl oligoglycosides; Gluco ronsäurederivaten; N-alkyl glucamides fatty acid; Protein hydrolyzates, esp special alkyl-modified protein hydrolyzates; low molecular weight chitosan compounds;  Zuckerestern; sorbitan; Amine oxides; and (ii) polymers nonionic surfactants such as fatty alcohol polyglycol ethers; Alkylphenolpoly glycol ethers; fatty acid polyglycol esters; Fettsäureamidpolyglykolethern; fatty amine polyglycol ethers; polyol fatty acid esters; Polysorbates.

As an ionic, i.e. H. cationic or anionic surfactants can according to the second embodiment of the method according to the invention the same ver bindings are used as in the first embodiment of the he inventive method. In this regard, the above explanations be referenced.

According to the second embodiment of the method according to the invention carries the content of surfactant in the prepared in step (a) Miniemulsion generally 0.1 to 15 wt .-%, preferably 0.3 up to 10% by weight, in particular 0.5 to 5% by weight, based on the mini pulp sion.

The production of the miniemulsion in process step (a) of the invention The method according to the second embodiment then closes in Process step (b) carrying out a polyaddition reaction between the monomers I and II in the presence of or to be encapsulated ß active ingredient and the surfactant in the miniemulsion provided in step (a), whereby an internal in-situ encapsulation or in-situ inclusion of the active ingredient in the polymer capsules, beads or droplets produced by polyaddition is effected.

As previously described, particle size and particle size are determined Division of the emulsified droplets in the mini emulsion, the particle size and Particle size distribution of the polymerized end products and is correct in essentially coincide with this. The polymer particles obtained can with Using dynamic light scattering in terms of their particle size and Monodispersity can be characterized.

In general, the reaction temperatures for the polyaddition are in Step (b) according to the second embodiment in particular about 35 to 100 ° C. about 40 to 90 ° C, preferably about 50 to 80 ° C.  

The reaction time is about 1 to about 24 h, in particular about 2 to 10 hours, preferably about 2 to about 5 hours.

The polyaddition can by thermal treatment or appropriate che Mix initiators are induced.

According to the second embodiment of the method according to the invention follows the polymerization in miniemulsion by polyaddition in the state of Mini emulsion, for which purpose difunctional and / or polyfunctional epoxides or Isocyanates with various suitable addition compounds, such as esp special di- or polyfunctional amines, alcohols, mercaptans, Acid anhydrides etc., in the presence of an active ingredient for the reaction brought, so that in this way an in-situ encapsulation or an in-situ Inclusion of the active ingredient in the Po produced by polyaddition lymer capsules, beads or droplets is effected. The poly formed Merisat (polymer) is special in the case of the second embodiment either an epoxy resin, which results from the addition of the di- or polyfunction addition compounds (amines, alcohols, mercaptans, carboxylic acid anhydride) results in the di- or polyfunctional epoxides, or a Polyurethane, which results from the addition of di- or polyfunctional alcohols the di- or polyfunctional isocyanates results, or a polyurine substance which results from the addition of di- or polyfunctional amines to the di- or polyfunctional isocyanates results.

Process steps (a) and (b) according to the second embodiment of the The method according to the invention can either be discontinuous or else be carried out continuously (e.g. as a batch process).

Even according to the second embodiment of the method according to the invention step (b) can optionally be followed by a step (c) connect, in which the active or active ingredient obtained in step (b) Polymer capsules, beads or droplets with known, the expert common methods can be separated or isolated. Here should no excessive shear forces on the polymer capsules, beads or -Droplets are exerted so that they are not damaged. Fiction suitable separation methods are, for example, freeze drying (Lyophilization) or spray drying under gentle conditions.  

The method according to the invention - both according to the first and the second embodiment - are therefore ideal for encapsulation or for the inclusion of active substances of the aforementioned type in poly mercapsules, globules or droplets.

The methods according to the invention - both according to the first as well as the second embodiment - show a number of advantages over conventional encapsulation methods:
The fact that the polymerization is non-radical has the advantage over known from the prior art, free-radical encapsulation process that the invention, sensitive active ingredients can be encapsulated or included.

The encapsulation of active and active ingredients by means of mini emulsion polymers Rization takes place in situ. Are active and during the polymerization reaction Active substances present, these are due to the reaction mechanism and of the present emulsion structure in the polymer network being formed and finally embedded in the resulting polymer particles. The addition the substances take place in the emulsification process. There are a variety of Store substances of all kinds, the storage of the active or active ingredients is particularly effective when the substances have bad what have solubility, d. H. are hydrophobic; but also amphiphilic substances can be emulsified and enclosed well.

The proportion of active and active ingredient can vary over a wide range become. The polymer capsules produced according to the invention have a large ß loading potential.

The choice of polymerization parameters enables targeted modification particle properties. By selecting suitable reaction partners can tailor the particle properties to the desired application be tailored. So you can tell about the type of bifunctional used len amines, mercaptans or alcohols and epoxides the properties of the re resulting polymers such as glass temperature, elasticity, stretch and stretch influence as well as melting or decomposition temperature. The type and Duration of initiation and the size of the miniemulsion droplets (mono loading) can control the molecular weight of the polymer formed, the degree of polymerization can also be limited by monofunctional additives become. In contrast, multifunctional monomers, in particular trifunctional and tetrafunctional ones  Epoxides and amines lead to cross-linking of the polymers and thus to a sharp increase in molecular weight. Leave with it there are also specific parameters of the polymer particles such as glass transition temperature and affect melting point.

A "controlled-release effect" can be achieved via the glass transition temperature of the particles aims to be. The exact setting of the glass temperature of the polymer particles is of crucial importance for later applications, since the ge targeted softening of the polymer matrix of the release (release) of the closed active and active ingredient can be activated. It shows, that the particles below the glass temperature are very stable and effective release of substances takes place extremely slowly. When the temperature rises above the glass temperature of the matrix softens the particles, and the release of the effect material is accelerated. This effect can e.g. B. used in ironing be to an increased fragrance release from the treated with the particles To produce laundry. By carefully selecting the starting monomers and the glass transition temperature of the resulting polymers Way of the hardness of the resulting polymer capsules the release ("re lease "). For example, in the case of soft polymers, for example sol chen with glass transition temperatures below room temperature, a re Relatively quick release of the encapsulated active ingredients, with harder bottom lymeren, e.g. B. those with glass transition temperatures above the room temperature, the release takes place more slowly, but through the action of Heat can be accelerated. When setting the glass temperatures to the desired value, however, the following must be observed: Since the glass temperature of the polymers in bulk - here measurement is carried out - is always higher than in dispersion because the surrounding water has an influence on the properties ten of the polymer chains, e.g. B. epoxy resin chains, this effect must the setting of the desired glass temperature are taken into account. The lowering of the glass temperature by water is approx. 20 to 40 ° C. Furthermore, the lowering of the glass temperature by the active or Active ingredient addition are taken into account; the lowering of the glass temperature due to the addition of oils as active ingredients about 20 to 60 ° C. One is ideal for a release temperature of 60 ° C Glass temperature of approx. 100 to 150 ° C of the bulk polymer.  

The present invention also relates to those according to the invention polymer cap produced according to the process seln, beads or droplets and their use.

The active or active produced by the process according to the invention substance-containing polymer capsules, beads or droplets generally have NEN average particle diameter from 10 nm to 500 nm, in particular from 40 nm to 450 nm, preferably from 50 nm to 400 nm.

The active or active produced by the process according to the invention polymer capsules, beads or droplets containing substance (synonymous as Polymer support systems or polymeric support systems referred to) contain at least one active ingredient included in a polymer matrix trix. The active or active ingredient content according to the ver drive manufactured active or active ingredient-containing polymer capsules, spheres or droplet is generally about 0.01 to about 80 wt .-%, ins especially about 0.1 to about 70% by weight, preferably about 1 to about 50 wt .-%, based on the total weight of the polymer capsules, beads or droplets.

The wall layers of those produced by the process according to the invention polymer capsules, beads or droplets containing active ingredient contain a polymer which is obtainable by non-radical mini min ion polymerization, especially polycondensation, preferably polyaddi tion, polymerized by non-radical mini-emulsion polymerization ble monomers, preferably epoxides and isocyanates and hereby under Polyaddition reacting compounds (amines, alcohols, mercaptans, Carboxylic anhydrides etc.), the active ingredient being hydrophobic or is amphiphile and is homogeneous with the starting monomer system lets. Preferably, the active ingredient can also be used with the Mix the polymer homogeneously. The polymer is in particular special around an epoxy resin, a polyurethane or a polyurea, depending on starting monomers used.

The surface, in particular the surface texture, the active or polymer capsules, beads or droplets containing active ingredient can be added if necessary, the surface modification being in situ rend polymerization or can be carried out subsequently. Such measures are familiar to the person skilled in the art.  

The modification of the surface properties of the particles can be chemical or done physically. It serves to substantiate the particles, in particular especially for laundry, fibers and fabrics or for skin and hair. A phy sical modification takes place through the choice of a suitable surfactant and / or polymers that are used directly in emulsion production or is subsequently added to the polymerized miniemulsion. Modification of the spray-dried material is also possible. A In-situ functionalization in the polymerization is carried out with additives functional monomers that have a corresponding surface properties lead shaft. Monomers with cationic, anionic or nonionic hydrophilic substituents can be used. The delayed one The release effect of the systems according to the invention can be coating of a polymer material or a salt be increased. The particles can also be attached to the Surface are masked, which z. B. for drug delivery in biologi environment or in vivo.

Substances suitable according to the invention for surface modification and -substantivation are suitable organic or inorganic compounds various types, such. B. cationic polymers, polyquaternized polymers, cationic biopolymers, cationic silicone oils, alkylamidoamines, quater nary ester compounds ("esterquats"), also in the form of their salts; to ionic and nonionic polymers such as polymers with anioni groups and anionic polyelectrolytes, naturally occurring Polymers, modified natural products, polysaccharides, biodegradable polymers, fully synthetic polymers, also in the form of their salts; inorganic Compounds such as zeolites, silicates, carbonates, hydrogen carbonates, soda, alkali and alkaline earth folds as well as phosphates and all before listed surfactants, in particular polymeric nonionic surfactants with EO / PO blocks as well as polyethylene glycol and polyethylene glycol derivatives.

Equally, those can be obtained by the method according to the invention made active or active ingredient-containing polymer capsules, beads or - droplets are stained. This can usually be done in that in addition to the active ingredients, dyes are also stored, which have previously been added to the mini emulsion.  

The possible uses of the method according to the invention manufactured active or active ingredient-containing polymer capsules, beads or - droplets are very numerous and extensive.

Thus, the active substances produced by the processes according to the invention or active ingredient-containing polymer carrier systems as delivery systems be used, especially in the field of cosmetics and personal care (e.g. for deodorants, hair treatment agents, etc.) in the pharmaceutical sector ze, in the processing of adhesives and / or in the area of washing and cleaning detergents (e.g. in dishwashing detergents, fabric softeners, detergents for the Wash at different temperatures etc.).

The present invention thus also relates to cosmetics, Personal care products, pharmaceuticals, adhesives or washing and cleaning agents agents containing the capsule systems according to the invention.

In particular, they can be produced by the processes according to the invention ten active or active ingredient-containing polymer capsules, beads or droplets as delivery systems for the controlled release of active ingredients fen can be used.

Further configurations and variations of the present invention are for the person skilled in the art can readily be seen when reading the description and re alisizable without leaving the scope of the present invention.

The present invention is based on the following exemplary embodiments illustrates which, however, in no way limit the invention.  

EMBODIMENTS

The glass temperatures were determined using a Per kin-Elmer DSC 7, heating rate 10 ° C / min.

example 1 Representation of bulk polymers

Various polymeric carrier particles that do not contain active or Active ingredient were loaded by polymerization (polyaddition) in miniemul sions according to the following recipes, the Mini emulsion polyaddition used amine was varied.

For this purpose, 16 g of a monomer mixture from the epoxides Epi kote® E 828 and Denacol® Ex-411 (ratio: 92.5% Epikote® E 828 and 7.5% Denacol® Ex-411) and the respective amine in a molar ratio of Epoxides to amine of 2: 1 under typical miniemulsion polymerization conditions implemented. The glass transition temperatures Tg of the resulting Polymer capsules are summarized in Table 1.

Table 1

Variation of the amine type in bulk polyaddition without loading with perfume oil

Example 2 Representation of bulk polymers loaded with perfume oil under Variation of the amine type

Under the same conditions as in Example 1, 16 g of monomers mixture (Epoxide Epikote® E 828 / Denacol® Ex-411 and respective amine) in molar ratio of epoxides to amine of 2: 1 in the presence of 1.6 g Perfume oil (orange oil) implemented.

Table 2

Variation of amine type in bulk polyaddition with 10% perfume oil loading

Example 3 Representation of bulk polymers loaded with perfume oil under Use of amine mixtures

Under the same conditions as in the previous examples 16 g monomer mixture (Epoxide Epikote® E 828 / Denacol® Ex-411 and each amine mixture) in a molar ratio of epoxides to amines of 2: 1 un ter presence of 1.6 g of perfume oil (orange oil) implemented.

Table 3

Use of amine mixtures in polyaddition

Example 4 Representation of bulk polymers loaded with perfume oil under Variation of the degree of loading

Under the same conditions as in the previous examples 16 g monomer mixture (Epoxide Epikote® E 828 / Denacol® Ex-411 and Amine) in a molar ratio of epoxides to amine of 2: 1 in the presence implemented by different amounts of perfume oil (orange oil).

Table 4

Variation of the loading level of perfume oil (orange oil)

Example 5 Representation of capsule systems loaded with perfume oil under Variation of the amine type

Polymeric carrier particles, loaded with perfume oil in situ, were prepared by polymerisation in mini-emulsion according to the following recipes:
Under the same conditions as in the preceding examples, 16 g of monomer mixture (Epoxide Epikote® E 828 / Denacol® Ex-411 and respective amine) were mixed in a molar ratio of epoxides to amine of 2: 1 in 120 ml of water in the presence of 3 g of surfactant and 1.6 g of perfume oil (orange oil) implemented. The pH was between 9 and 10.

Table 5

Variation of the amine type in the polyaddition in mini emulsion

Example 6 Representation of capsule systems loaded with perfume oil under Use of amine mixtures

Polymeric carrier particles, loaded with perfume oil in situ, were prepared by polymerisation in mini-emulsion according to the following recipes:
Under the same conditions as in the preceding examples, 16 g of monomer mixture (Epoxide Epikote® E 828 / Denacol® Ex-411 and amine mixture D 2000 / D 230) were mixed in a molar ratio of epoxides to amines of 2: 1 in 120 ml of water in the presence of 3 g of surfactant and 1.6 g of perfume oil (orange oil) implemented. The pH was between 9 and 10.

Table 6

Variation of the mixing ratio of the amines Jeffamine® D 2000 and Jeffamine® D 230 in the polyaddition in miniemulsion

Example 7 Representation of capsule systems loaded with perfume oil under Use of amine mixtures

Polymeric carrier particles, loaded with perfume oil in situ, were prepared by polymerisation in mini-emulsion according to the following recipes:
Under the same conditions as in the preceding examples, 16 g of monomer mixture (Epoxide Epikote® E 828 / Denacol® Ex-411 and amine mixture D 2000 / isophoronediamine) were mixed in a molar ratio of epoxides to amines of 2: 1 in 120 ml of water in the presence of 3 g Surfactant and 1.6 g of perfume oil (orange oil) implemented. The pH was between 9 and 10.

Table 7

Variation of the mixing ratio of the amines Jeffamine® D 2000 and isophoronediamine in the polyaddition in miniemulsion

Will one of the manufactured in the previous embodiments Capsule dispersions containing particles with an oil-like fragrance, for example applied to a fabric via a liquid fabric softener, so an improved fragrance effect is achieved when ironing the fabric.

Claims (63)

1. A process for the preparation of active or active substance-containing polymer capsules, beads or droplets, the process comprising the following process steps:

• a) Provision of a mini emulsion comprising:

• compounds polymerizable by non-radical emulsion polymerization (monomers),
• - At least one active or active ingredient to be encapsulated or enclosed and
• - At least one surface-active substance (surfactant) for stabilizing the miniemulsion, in particular selected from the group of
  • a) nonionic surfactants, in particular non-polymeric, preferably low molecular weight nonionic surfactants, and
  • b) ionic surfactants;

• a) Carrying out a non-radical polymerization reaction in the miniemulsion provided under step (a), this thereby causing in-situ encapsulation or in-situ inclusion of the active ingredient in the polymer capsules, beads or droplets produced by non-radical polymerization reaction becomes; and
• b) subsequently, if appropriate, separating off the polymer capsules, beads or droplets containing active ingredient or active ingredient obtained in this way,

characterized in that the active ingredient is hydrophobic or amphiphilic and can be mixed homogeneously with the monomer system. 2. The method according to claim 1, wherein the active ingredient is also can be mixed homogeneously with the polymer system produced in step (b). 3. The method according to claim 1 or 2, wherein the active ingredient in the is essentially water-insoluble or at least in the aqueous phase is hardly soluble.   4. The method according to claim 3, wherein the active ingredient in the aqueous phase to less than 10%, preferably to less than 5%, in particular less than 1%, is soluble. 5. The method according to any one of claims 1 to 4, wherein the active or Active ingredient in organic media and solvents, especially in the monomers, is soluble or dispersible. 6. The method according to any one of claims 1 to 5, wherein the active or Active substance is present as a liquid under reaction conditions. 7. The method according to any one of claims 1 to 5, wherein the active or Active ingredient is present as a solid under reaction conditions. 8. The method according to any one of claims 1 to 7, wherein the active or Active ingredient is selected from the group of fragrances; Oil like essential oils, perfume oils, care oils and silicone oils; pharmaceutically table-active substances such as antibacterial, antiviral or fungicidal drugs; Antioxidants and biologically active substances; vitami nen and vitamin complexes; Enzymes and enzymatic systems; cosmetically active substances; wash and cleaning active substance Zen; biogenic agents and genes; Polypeptides and viruses; Protei nen and lipids; Waxing and fats; Foam inhibitors; graying inhibitors and color protection agents; Soil-repellent active ingredients; Bleach activators and optical brighteners; amines; as well as mixtures of the compounds listed above, in particular also mixtures with dyes or coloring substances. 9. The method according to any one of claims 1 to 8, wherein the active or Active ingredient content in the miniemulsion 0.01 provided in step (a) up to 45% by weight, preferably 0.1 to 25% by weight, in particular 1 to 15% by weight, is based on the mini emulsion. 10. The method according to any one of claims 1 to 9, wherein the monomers by polycondensation reaction, in particular by polyaddition reaction, are polymerizable.   11. The method according to any one of claims 1 to 10, wherein the monomers are hydrophobic or amphiphilic. 12. The method according to any one of claims 1 to 11, wherein the monomers in are essentially water-insoluble or at least in the aqueous phase are hardly soluble. 13. The method of claim 12, wherein the monomers in the aqueous Phase less than 10%, preferably less than 5%, in particular less than 1% of which are soluble. 14. The method according to any one of claims 1 to 13, wherein the Monmenge holds 1 to 45% by weight in the mini emulsion provided in step (a), is preferably 3 to 25% by weight, in particular 5 to 15% by weight, based on the mini emulsion. 15. The method according to any one of claims 1 to 14, wherein the interfaces active substance is a non-polymeric nonionic surfactant and esp is selected from the group of alkoxylated, preferred wise ethoxylated fatty alcohols, alkylphenols, fatty amines and fat acid amides; alkoxylated triglycerides, mixed ethers and mixed forma len; optionally partially oxidized alk (en) yl oligoglycosides; Gluco ronsäurederivaten; N-alkyl glucamides fatty acid; protein hydrolysates, especially alkyl modified protein hydrolyzates; low molecular weight chitosan; Zuckerestern; sorbitan; Amine oxides. 16. The method according to any one of claims 1 to 14, wherein the interfaces active substance is a cationic surfactant and in particular selected is from the group of quaternary ammonium compounds such as Dime ethyl distearyl ammonium chloride (CTMA-Cl); Esterquats, in particular quaternized fatty acid trialkanolamine ester salts; Salt long chain primary amines; quaternary ammonium compounds such as hexadecyl trimethyl ammonium chloride; Cetrimonium chloride or lauryldimethyl benzyl ammonium chloride.   17. The method according to any one of claims 1 to 14, wherein the interfaces active substance is an anionic surfactant and in particular selected is from the group of soaps; alkylbenzenesulfonates; Alkansulfona th; olefin; alkyl ether; Glycerinethersulfonaten; α-methyl ester sulfonates; sulfofatty; alkyl sulfates; fatty alcohol ether sulfates; glycerol ether; Fettsäureethersulfaten; hydroxy mischethersulfaten; Monoglyceride (ether) sulfates; fatty acid amide sulphates (ether); Mono- and dialkyl sulfosuccinates; Mono- and dialkyl sulfosuccinamates; sulfotriglycerides; amide soaps; ether and their salts; Fettsäureisothionaten; Fettsäuresarcosinaten; grease säuretauriden; N-acylamino acids such as acyl lactylates, acyl tartrates, Acyl glutamates and acyl aspartates; oligoglucoside sulfates; per fatty acid condensates, especially vegetable products on white zenbasis; Alkyl (ether) phosphates. 18. The method according to any one of claims 1 to 17, wherein the content of surfactant in the mini provided in step (a) emulsion 0.1 to 15 wt .-%, preferably 0.3 to 10 wt .-%, in particular whose 0.5 to 5 wt .-%, based on the mini emulsion. 19. The method according to any one of claims 1 to 18, wherein it is in the Mi no emulsion around an essentially watery, through the interfaces active substance stabilized emulsion of monomers and active or Active ingredient (s) with a particle size of the emulsified droplets of 10 nm to 500 nm, in particular from 40 nm to 450 nm, preferably from 50 nm to 400 nm. 20. A process for producing polymer capsules, beads or droplets containing active ingredients by miniemulsion polyaddition, the process comprising the following process steps:

• a) Provision of a mini emulsion comprising:

• at least one di- or polyfunctional epoxide or isocyanate (monomer I),
• at least one compound which reacts with the di- or polyfunctional epoxide or isocyanate (monomer I) with polyaddition (monomer II),
• - At least one active or active ingredient to be encapsulated or enclosed and
• - At least one surface-active substance (surfactant) for stabilizing the mini emulsion;

• a) Carrying out a polyaddition reaction between the monomers I and II in the presence of the active or active ingredient to be encapsulated or enclosed and the surface-active substance in the miniemulsion provided under step (a), thereby encapsulating in situ or in -in situ inclusion of the active ingredient or active ingredient in the polymer capsules, spheres or droplets produced by polyaddition; and
• b) subsequently, if appropriate, separating off the polymer capsules, beads or droplets containing active ingredient or active ingredient obtained in this way,

characterized in that the active ingredient is hydrophobic or amphiphilic and can be mixed homogeneously with the monomer system. 21. The method according to claim 20, wherein the active or active ingredient is itself can be mixed homogeneously with the polymer system produced in step (b). 22. The method of claim 20 or 21, wherein the polymer system is a Epoxy resin, a polyurethane or a polyurea. 23. The method according to any one of claims 20 to 22, wherein the active or Active ingredient is essentially water-insoluble or at least in the aqueous phase is only sparingly soluble. 24. The method according to claim 23, wherein the active ingredient in the aqueous phase to less than 10%, preferably to less than 5%, in particular less than 1%, is soluble. 25. The method according to any one of claims 20 to 24, wherein the active or Active ingredient in organic media and solvents, especially in the monomers, is soluble or dispersible.   26. The method according to any one of claims 20 to 25, wherein the active or Active substance is present as a liquid under reaction conditions. 27. The method according to any one of claims 20 to 25, wherein the active or Active ingredient is present as a solid under reaction conditions. 28. The method according to any one of claims 20 to 27, wherein the active or Active ingredient is selected from the group of fragrances; Oil like essential oils, perfume oils, care oils and silicone oils; pharmaceutically table-active substances such as antibacterial, antiviral or fungicidal drugs; Antioxidants and biologically active substances; vitami nen and vitamin complexes; Enzymes and enzymatic systems; cosmetically active substances; wash and cleaning active substance Zen; biogenic agents and genes; Polypeptides and viruses; Protei nen and lipids; Waxing and fats; Foam inhibitors; graying inhibitors and color protection agents; Soil-repellent active ingredients; Bleach activators and optical brighteners; amines; as well as mixtures of the compounds listed above, in particular also mixtures with dyes or coloring substances. 29. The method according to any one of claims 20 to 28, wherein the active or Active ingredient content in the miniemulsion 0.01 provided in step (a) up to 45% by weight, preferably 0.1 to 25% by weight, in particular 1 to 15% by weight, is based on the mini emulsion. 30. The method according to any one of claims 20 to 29, wherein the monomers I and / or II are hydrophobic or amphiphilic. 31. The method according to any one of claims 20 to 30, wherein the monomers I and / or II essentially water-insoluble or at least in the aq phase are difficult to dissolve. 32. The method according to claim 31, wherein the monomers I and / or II in the aqueous phase to less than 10%, preferably to less than 5%, in particular less than 1% are soluble.   33. The method according to any one of claims 20 to 32, wherein the content of Monomers I and II in the mini emulsion 1 provided in step (a) up to 45% by weight, preferably 3 to 25% by weight, in particular 5 to 15% by weight, is based on the mini emulsion. 34. The method according to any one of claims 20 to 33, wherein the molar Ver Ratio of monomers I to monomers II generally about 2: 1 is. 35. The method according to any one of claims 20 to 34, wherein the monomer I is a di- or polyfunctional isocyanate and that with the di- or po Compound reacting lyfunctional isocyanate with polyaddition (Monomer II) in particular is selected from the group of (i) di and polyfunctional amines and mixtures thereof, (ii) di- and poly functional alkanols and mixtures thereof and (iii) mixtures of the aforementioned connections. 36. The method according to any one of claims 20 to 34, wherein the monomer I is a di- or polyfunctional epoxy and that with the di- or poly functional epoxy compound reacting with polyaddition (Monomer II) in particular is selected from the group of (i) di and polyfunctional amines and mixtures thereof, (ii) di- and poly functional alkanols and their mixtures, (iii) di- and polyfunction nell mercaptans and their mixtures, (iv) di- and polyfunctional len carboxylic acid anhydrides and their mixtures as well as (v) mixtures gene of the aforementioned compounds. 37. The method of claim 36, wherein the monomer I is a difunctional epoxide and is in particular derived from bisphenol A such as bisphenol-A diglycidyl ether or an epoxy of the epichlorohydrin-substituted bisphenol type is like the epoxide of the formula
38. The method according to claim 36, wherein the monomer I is a trifunctional epoxide, in particular an epoxide of the formula
39. The method of claim 36, wherein the monomer I is a tetrafunctional epoxy, in particular an epoxy of the formula
40. The method according to any one of claims 36 to 39, wherein the with the di- or polyfunctional epoxy with polyaddition reactive compound tion (monomer II) is a di- or polyfunctional amine and in particular is selected from the group of (i) optionally substituted ized alkyl diamines, especially those with terminal amino groups such as 1,12-diaminododecane or optionally cyanoethylated Trimethylhexamethylendiaminen; (ii) optionally substituted bis- (aminocycloalkyl) alkanes such as 4,4'-diaminodicyclohexylmethane or isophoron diamines; (iii) optionally substituted bis (aminoaryl) - alkanes such as 4,4'-diaminobibenzyl or 4,4'-diaminodiphenylmethane; (iv) polyoxyalkylene diamines with molecular weights up to about 5,000 g / mol, in particular polyoxyalkylene diamines with polyoxyethylene and / or polyoxypropylene units; (v) Tri and tetrafunctional ami such as N, N, N ', N'-tetraglycidyldiamino-4,4'-diphenylmethane or ent talking multifunctional prepolymers; (vi) polyfunctional Amines such as chitosan and chitosan derivatives, polyethyleneimines, cat ionic amine polymers such as polydiallyldimethylammonium chloride (Poly-DADMAC) and reaction products of polylactides or poly glycolites with isophorone diisocyanate. 41. The method according to any one of claims 36 to 39, wherein the with the di- or polyfunctional epoxy with polyaddition reactive compound tion (monomer II) is a di- or polyfunctional alkanol and in particular is special 2,2-bis (4-hydroxyphenyl) propane (bisphenol A).   42. The method according to any one of claims 36 to 39, wherein the with the di- or polyfunctional epoxy with polyaddition reactive compound tion (Monomer II) is a difunctional or polyfunctional mercaptan and ins particular is selected from the group of optionally substituted ized alkyldithiols (dithioalkanes), preferably those with terminal thiol groups (SH groups) such as 1,6-hexanedithiol. 43. The method according to any one of claims 20 to 42, wherein the interfaces active substance is a cationic surfactant and in particular selected is from the group of quaternary ammonium compounds such as Dime ethyl distearyl ammonium chloride (CTMA-Cl); Esterquats, in particular quaternized fatty acid trialkanolamine ester salts; Salt long chain primary amines quaternary ammonium compounds such as hexadecyl trimethyl ammonium chloride; Cetrimonium chloride or lauryldimethyl benzyl ammonium chloride. 44. The method according to any one of claims 20 to 42, wherein the interfaces active substance is an anionic surfactant and in particular selected is from the group of soaps; alkylbenzenesulfonates; Alkansulfona th; olefin; alkyl ether; Glycerinethersulfonaten; α-methyl ester sulfonates; sulfofatty; alkyl sulfates; fatty alcohol ether sulfates; glycerol ether; Fettsäureethersulfaten; hydroxy mischethersulfaten; Monoglyceride (ether) sulfates; fatty acid amide sulphates (ether); Mono- and dialkyl sulfosuccinates; Mono- and dialkyl sulfosuccinamates; sulfotriglycerides; amide soaps; ether and their salts; Fettsäureisothionaten; Fettsäuresarcosinaten; grease säuretauriden; N-acylamino acids such as acyl lactylates, acyl tartrates, Acyl glutamates and acyl aspartates; oligoglucoside sulfates; per fatty acid condensates, especially vegetable products on white zenbasis; Alkyl (ether) phosphates. 45. The method according to any one of claims 20 to 42, wherein the interfaces active substance is a nonionic surfactant and the is selected Group of (i) non-polymeric nonionic surfactants such as alkoxylating ten, preferably ethoxylated fatty alcohols, alkylphenols, Fettami nen and fatty acid amides; alkoxylated triglycerides, mixed ethers and Mixed formals; optionally partially oxidized alk (en) yl oligoglycosides;  Glucoronsäurederivaten; N-alkyl glucamides fatty acid; protein hydrolyzates, especially alkyl-modified protein hydrolyzates; never the molecular chitosan compounds; Zuckerestern; sorbitan; Amine oxides; and (ii) polymeric nonionic surfactants such as fatty alcohols holpolyglykolethern; alkylphenol polyglycol; Fettsäurepolyglykol esters; Fettsäureamidpolyglykolethern; fatty amine polyglycol ethers; poly olfettsäureestern; Polysorbates. 46. The method according to any one of claims 20 to 45, wherein the content of surfactant in the mini provided in step (a) emulsion 0.1 to 15 wt .-%, preferably 0.3 to 10 wt .-%, in particular whose 0.5 to 5 wt .-%, based on the mini emulsion. 47. The method according to any one of claims 20 to 46, wherein it is the Mini emulsion around an essentially watery, through the interfaces active substance stabilized emulsion of monomers and active or Active ingredient (s) with a particle size of the emulsified droplets of 10 nm to 500 nm, in particular from 40 nm to 450 nm, preferably from 50 nm to 400 nm. 48. The method according to any one of claims 1 to 47, wherein the reaction tem temperature for the polymerization, especially polycondensation, preferred wise polyaddition, about 20 to 100 ° C, preferably about 40 to 90 ° C, in particular about 50 to 80 ° C. 49. The method according to any one of claims 1 to 48, wherein the reaction time is about 0.01 to about 24 hours, especially about 0.1 to 10 hours preferably about 1 to about 5 hours. 50. The method according to any one of claims 1 to 49, wherein the active or active ingredient-containing polymer capsules, beads or droplets medium Particle diameter from 10 nm to 500 nm, in particular from 40 nm up to 450 nm, preferably from 50 nm to 400 nm. 51. The method according to any one of claims 1 to 50, wherein the active or active ingredient-containing polymer capsules, beads or droplets an Ak active or active ingredient content of about 0.01 to about 80 wt .-%, in particular  from about 0.1 to about 70% by weight, preferably from about 1 to about 50 wt .-%, based on the total weight of the poly mercapsules, globules or droplets. 52. The method according to any one of claims 1 to 51, wherein the surface of the polymer capsules or spheres containing active ingredient or active ingredient droplet is modified, the surface modification in situ takes place during the polymerization or is carried out subsequently. 53. The method according to any one of claims 1 to 52 for encapsulation or for the inclusion of active or active substances in polymer capsules, -beads or droplets. 54. Active polymer capsules, beads or droplets chen, obtainable by the process according to claims 1 to 53. 55. Active or active ingredient-containing polymer capsules, beads or -Droplets that contain at least one active ingredient in a bottom forming the capsule, bead or droplet material lymer matrix, and the wall layers of which comprise a polymer sen, the polymer is obtainable by non-radical mini emulsion polymerization, especially polycondensation, preferably Polyaddition, from by non-radical mini emulsion polymerization polymerizable monomers and hereby react with polyaddition renden compounds, characterized in that the active or Active ingredient is hydrophobic or amphiphilic and deals with the monomer system can be mixed homogeneously. 56. Active or active ingredient-containing polymer capsules, beads or droplets 56. The claim 55, wherein the active ingredient is also associated with the Allows polymer to mix homogeneously. 57. Polymer capsules, beads or droplets containing active ingredient 56 according to claim 55 or 56, wherein the polymer is an epoxy resin Is polyurethane or a polyurea.   58. Active polymer capsules, beads or droplets according to one of claims 55 to 57, characterized by medium Particle diameter from 10 nm to 500 nm, in particular from 40 nm to 450 nm, preferably from 50 nm to 400 nm. 59. Active polymer capsules, beads or droplets according to one of claims 55 to 58, characterized by an active or active ingredient content of about 0.01 to about 80 wt .-%, in particular from about 0.1 to about 70% by weight, preferably from about 1 to about 50% by weight, based on the total weight of the polymer capsules, -beads or droplets. 60. Use of the active or active ingredient-containing polymer carrier steme according to claims 55 to 59 as delivery systems, in particular others in the field of cosmetics and personal care, in the field of phar macie, in adhesive processing and / or in the area of washing and detergents. 61. Use according to claim 60 for the controlled release of Active ingredients. 62. Use according to claim 61, wherein the control of the release of the Active ingredients through the control of the glass transition temperature of the polymers. 63. Cosmetics, personal care products, pharmaceuticals, adhesives or detergents and detergents containing active or active ingredient-containing polymer Capsules, beads or droplets according to claims 54 to 59.